1. Field of the Invention
The present invention relates to oral veterinary pharmaceuticals containing pentoxifylline. More particularly, the present invention is directed to treating equine navicular disease with Pentoxifylline.
2. Discussion of Background and Material Information
Navicular disease has been recognized clinically for several hundred years and attempts to describe the pathology of this condition are on record for over 200 years. Traditionally navicular disease has been regarded as a degenerative (arthrotic) or inflammatory (arthritic, bursitic) process. Nevertheless, a vascular etiology was proposed as early as 1885 by Wally, and angiography was first performed in 1938 by Jones in an attempt to illustrate thrombosis of the digital arteries. More recently, Colles has proposed that the pain of navicular disease is due to ischemic bone necrosis caused by thrombosis of the distal nutrient arteries of the navicular bone. Thrombosis was demonstrated in angiographic studies and on histopathology, as a significant finding in horses with navicular disease. Independent studies have supported a vascular etiology of navicular disease.
Pentoxifylline ((1-(5-oxohexyl)-3, 7-dimethylxanthine) is a methylxanthine derivative, for example disclosed in U.S. Pat. No. 3,422,107, MOHLER et al., which has emerged at the forefront in the treatment of chronic occlusive arterial disease (COAD) in man. The most common symptom of COAD is intermittent claudication. Decreased red blood cell flexibility, arterial occlusion and artherosclerosis are the cardinal pathological features of intermittent claudication.
Pentoxifylline is classified as a haemorheological agent. It improves perfusion in ischemic tissues by at least three distinct mechanisms. First, pentoxifylline enhances red cell deformability and decreases red cell rigidity resulting in reduced viscosity of the blood. This allows the red cells to pass through narrow capillary networks. Secondly, pentoxifylline inhibits platelet aggregation. Thirdly, pentoxifylline promotes fibrinolysis. In combination, these actions serve to increase the blood flow through diseased vessels and into compromised tissues.
The effect of pentoxifylline in increasing red blood cell membrane flexibility is produced through inhibition of phosphodiesterase, which in turn causes increased intracellular cyclic-AMP and ATP levels. Pentoxifylline has a direct action on platelets to decrease aggregability and also causes release of prostacyclin (P.sub.g I.sub.2) from endothelial cells. Prostacyclin is the most potent inhibitor of platelet aggregation. The fibrinolytic action of pentoxifylline is mediated through interaction with P.sub.g E.sub.1.
U.S. Pat. Nos. 4,383,997 and 4,500,530, BOUCHER, are directed to a method of treating horses to inhibit or reduce increases in crenated red blood cells during exercise by administering to the animal a compound which inhibits influx of extracellular Ca++ into red blood cells, or enhances ATP content of ATP-depleted red blood cells. Examples of compounds disclosed which increase intracellular ATP include Pentoxifylline.
U.S. Pat. No. 4,511,557, GAURI is directed to a pharmaceutical compositions based on vasoactive compounds in combination with certain biological active ingredients which are capable of promoting oxygen supply which is preferably a dialysate concentrate obtained from the proteinized calf blood. Pentoxifylline is disclosed as an example of the vasoactive compound suitable for purposes of use in formulating this composition.
U.S. Pat. No. 3,928,609, BEHRAKIS relates to a vehicle for pharmaceuticals which improves absorption of the active agent in the alimentary tract. It is disclosed that compositions which include these type of compounds, such as theophylline, have been used for the treatment in the veterinary field as an asthma remedy and heart stimulant for animals.
U.S. Pat. No. 4,460,772, BENOVIC et al., relates to theophylline derivatives pertaining to immunoassays for determining theophylline in liquid media such as biological fluids.